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The Placebo Response in the Treatment of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis

Cho, Hyong Jin MD; Hotopf, Matthew PhD; Wessely, Simon MD

doi: 10.1097/01.psy.0000156969.76986.e0

Objective: The placebo response is conventionally asserted to be high in chronic fatigue syndrome (CFS) because of the latter’s subjective nature and obscure pathogenesis, but no systematic review of placebo responses has been undertaken. We report such a study. Patient expectation is known to be important in the placebo response. It is also known that CFS patients attending specialist clinics often have strong physical attributions regarding causation and hence skepticism about psychological or psychiatric interventions. If so, the placebo response in CFS may be influenced by the type of intervention according to its perceived rationale. We aimed to estimate the summary placebo response in clinical trials of CFS and to determine whether intervention type influences the placebo response in CFS.

Methods: We searched Medline, Embase, Cochrane Library, PsychInfo, and the references of the identified articles, and contacted experts for controlled trials (randomized or nonrandomized) of any intervention on CFS patients reporting the placebo response as a clinical improvement in physical or general outcomes. Data were extracted from the articles and validity assessment conducted by one reviewer and checked by a second. Meta-analysis and metaregression were performed.

Results: The pooled placebo response was 19.6% (95% confidence interval, 15.4–23.7), lower than predicted and lower than in some other medical conditions. The meta-regression revealed that intervention type significantly contributed to the heterogeneity of placebo response (p = .03).

Conclusion: In contrast with the conventional wisdom, the placebo response in CFS is low. Psychological-psychiatric interventions were shown to have a lower placebo response, perhaps linked to patient expectations.

CFS = chronic fatigue syndrome; CCT = controlled clinical trial; CBT = cognitive-behavioral therapy; CI = confidence interval; GET = graded exercise therapy.

From the Section of General Hospital Psychiatry, Institute of Psychiatry, King’s College London, United Kingdom.

Dr. Cho is sponsored by a scholarship from CAPES-Brazilian Ministry of Education.

Address correspondence and reprint requests to Dr. Hyong Jin Cho, Section of General Hospital Psychiatry, Institute of Psychiatry, King’s College London, P. O. Box 62, Weston Education Centre, 10 Cutcombe Road, London SE5 9RJ, United Kingdom. E-mail:

Received for publication March 26, 2004; revision received November 9, 2004.

Copyright © 2005 by American Psychosomatic Society
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